Journal
BIOCHEMICAL JOURNAL
Volume 442, Issue -, Pages 293-302Publisher
PORTLAND PRESS LTD
DOI: 10.1042/BJ20110282
Keywords
c-Jun N-terminal kinase (JNK); invasion; matrix metalloproteinase (MMP); mesothelin; mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK); ovarian cancer
Categories
Funding
- Min-Sheng General Hospital, Taoyuan
- National Science Committee of Taiwan [97-2314-B-002-064-MY3]
- Department of Medical Research of National Taiwan University Hospital
- National Taiwan University Hospital [97-000837]
- Taiwan-National Taiwan University Hospital [97MSN05]
Ask authors/readers for more resources
Ovarian cancer has one of the highest mortalities in malignancies in women, but little is known of its tumour progression properties and there is still no effective molecule that can monitor its growth or therapeutic responses. MSLN (mesothelin), a secreted protein that is overexpressed in ovarian cancer tissues with a poor clinical outcome, has been previously identified to activate PI3K (phosphoinositide 3-kinase)/Akt signalling and inhibit paclitaxel-induced apoptosis. The present study investigates the correlation between MSLN and MMP (matrix metalloproteinase)-7 in the progression of ovarian cancer, and the mechanism of MSLN in enhancing ovarian cancer invasion. The expression of MSLN correlated well with MMP-7 expression in human ovarian cancer tissues. Overexpressing MSLN or ovarian cancer cells treated with MSLN showed enhanced migration and invasion of cancer cells through the induction of MMP-7. MSLN regulated the expression of MMP-7 through the ERK (extracellular-signal-regulated kinase) 1/2, Akt and JNK (c-Jun N-terminal kinase) pathways. The expression of MMP-7 and the migrating ability of MSLN-treated ovarian cancer cells were suppressed by ERK1/2-or JNK-specific inhibitors, or a decoy AP-1 (activator protein I) oligonucleotide in in vitro experiments, whereas in vivo animal experiments also demonstrated that mice treated with MAPK (mitogen-activated protein kinase)/ERK- or JNK-specific inhibitors could decrease intratumour MMP-7 expression, delay tumour growth and extend the survival of the mice. In conclusion, MSLN enhances ovarian cancer invasion by MMP-7 expression through the MAPK/ERK and JNK signal transduction pathways. Blocking the MSLN-related pathway could be a potential strategy for inhibiting the growth of ovarian cancer.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available